ROLE OF KLOTHO GENE IN RENAL PROTECTION

与喂食低盐（0.3%NaCl）饮食的大鼠相比，喂食高盐（8%NaCl）饮食的Dahl盐敏感性高血压（Dahl-S）大鼠肾脏中klotho mRNA的表达显著降低（n=7）。每周一次持续3周的klotho基因递送诱导注射部位处的klotho mRNA表达。氢乙定，一种氧化荧光染料，被用来评估超氧化物的水平在原位。肌内诱导klotho基因降低了主动脉中超氧化物的产生，导致内皮功能障碍从对照大鼠的43± 6%恢复到61± 9%（n=6，p<0.05）。收缩压由262±11 mmHg降至234±6 mmHg（P<0.05）。此外，klotho基因递送将血管周围纤维化从0.031±0.002 mm^2改善至0.011±0.001 mm^2，并将白蛋白尿从2.5±0.4 g/天减少至0.31±0.14 g/天（n=8，p<0.05）。我们认为，诱导klotho基因的表达与改善内皮功能可能是一个潜在的新的治疗策略，由高血压引起的肾功能衰竭。

The expression of klotho mRNA in the kidney was significantly reduced in Dahl salt-sensitive hypertensive (Dahl-S) rats fed high salt (8% NaCl) diet as compared to those fed low salt (0.3% NaCl) diet (n=7). The klotho gene delivery once a week for 3 weeks induced klotho mRNA expression at the injection site. Hydroethidine, an oxidative fluorescent dye, was used to evaluate the levels of superoxide in situ. Intramuscular induction of the klotho gene decreased in superoxide production in the aorta, resulting in restoration of endothelial dysfunction from 43±6 % to 61±9 % of control rats (n=6, p<0.05). At the same time, systolic blood pressure was reduced from 262±11 mmHg to 234±6 mmHg (p<0.05). Furthermore, klotho gene delivery improved perivascular fibrosis from 0.031±0.002 to 0.011±0.001 mm^2 and reduced albuminuria from 2.5±0.4 to 0.31±0.14 g/day (n=8, p<0.05).Our study indicates that intramusclar delivery of the klotho gene reduces oxidative stress and protects the vascular endothelium in Dhal-S rats. We suggest that induction of the klotho gene expression associated with the improvement of the endothelial function may be a potential novel therapeutic strategy for renal failure induced by hypertension.